tbuckley/cabot-search huggingface dataset:
Reporting of Immunotherapy and Biologic Therapy in the National Cancer Database
Authors: J. Bryan Iorgulescu
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Tobacco Product Use Among Adults – United States, 2021
Authors: Monica E. Cornelius, Caitlin G. Loretan, Ahmed Jamal, Brittny C. Davis Lynn, Margaret Mayer, Iris C. Alcantara, Linda Neff
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Commercial cigarette smoking among U.S. adults has declined during the preceding 5 decades (1,2); however, tobacco product use remains the leading cause of preventable disease and death in the United States, and some populations continue to be disproportionately affected by tobacco use (1,2). To assess recent national estimates of commercial tobacco use among U.S. persons aged ≥18 years, CDC, the Food and Drug Administration (FDA), and the National Cancer Institute analyzed 2021 National Health Interview Survey (NHIS) data. In 2021, an estimated 46 million U.S. adults (18.7%) reported currently using any tobacco product, including cigarettes (11.5%), e-cigarettes (4.5%), cigars (3.5%), smokeless tobacco (2.1%), and pipes (including hookah)* (0.9%).† Among those who used tobacco products, 77.5% reported using combustible products (cigarettes, cigars, or pipes), and 18.1% reported using two or more tobacco products.§ The prevalence of current use of any tobacco product use was higher among the following groups: men; persons aged <65 years; persons of non-Hispanic other races; non-Hispanic White (White) persons¶; residents of rural (nonmetropolitan) areas; financially disadvantaged (income-to-poverty ratio = 0-1.99); lesbian, gay, or bisexual (LGB) persons; those uninsured or enrolled in Medicaid; adults whose highest level of education was a general educational development (GED) certificate; who had a disability; and who had serious psychological distress. Continued surveillance of tobacco product use, implementation of evidence-based tobacco control strategies (e.g., hard-hitting media campaigns, smoke-free policies, and tobacco price increases), conducting linguistically and culturally appropriate educational campaigns, and FDA regulation of tobacco products will aid in reducing tobacco-related disease, death, and disparities among U.S. adults (3,4).
<i>Salmonella</i> Outbreaks Associated with Not Ready-to-Eat Breaded, Stuffed Chicken Products — United States, 1998–2022
Authors: Laura Ford, Sean Buuck, Taylor Eisenstein, Andrea Cote, Zachary D. McCormic, Selena Kremer-Caldwell, Bonnie Kissler, Matthew Forstner, Alida Sorenson, Matthew E. Wise, Kirk Smith, Carlota Medus, Patricia M. Griffin, Misha Robyn
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Not ready-to-eat (NRTE) breaded, stuffed chicken products (e.g., chicken stuffed with broccoli and cheese) typically have a crispy, browned exterior that can make them appear cooked.These products have been repeatedly linked to U.S. salmonellosis outbreaks, despite changes to packaging initiated in 2006 to identify the products as raw and warn against preparing them in a microwave oven (microwave) (1-4).On April 28, 2023, the U.S. Department of Agriculture proposed to declare Salmonella an adulterant* at levels of one colony forming unit per gram or higher in these products (5).Salmonella outbreaks associated with NRTE breaded, stuffed chicken products during 1998-2022 were summarized using reports in CDC's Foodborne Disease Outbreak Surveillance System (FDOSS), outbreak questionnaires, web postings, and data from the Minnesota Department of Health (MDH) † and the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS).Eleven outbreaks were identified in FDOSS.Among cultured samples from products obtained from patients' homes and from retail stores during 10 outbreaks, a median of 57% of cultures per outbreak yielded Salmonella.The NRTE breaded, stuffed chicken products were produced in at least three establishments.§ In the seven most recent outbreaks, 0%-75% of ill respondents reported cooking the product in a microwave and reported that they thought the product was sold fully cooked or did not know whether it was sold raw or fully cooked.Outbreaks associated with these products have occurred despite changes to product labels that better inform consumers that the products are raw and provide instructions on safe preparation, indicating that consumer-targeted interventions are not sufficient.Additional Salmonella controls at the manufacturer level to reduce contamination in ingredients might reduce illnesses attributable to NRTE breaded, stuffed chicken products.* The circumstances under which a poultry product is considered adulterated are defined in the Poultry Products Inspection Act, which includes several conditions that result in a product's being unsafe or harmful to health (21 U.S.C. 453 [g]).† With one exception, MDH first identified and led the investigation for every outbreak described in this report, and also provided CDC with additional outbreak reports for each of the 10 outbreaks.§ An establishment at which inspection of the slaughter of poultry, or the processing of poultry products, is maintained under the authority of 21 U.S.C.Chapter 10 Sect.453p, as determined by the U.S.
Intracellular trafficking of HLA-E and its regulation
Authors: Wanlin He, Ester Gea-Mallorquí, Huw Colin-York, Marco Fritzsche, Geraldine M. Gillespie, Simon Brackenridge, Persephone Borrow, Andrew J. McMichael
Journal: The Journal of Experimental Medicine (2023)

Interest in MHC-E–restricted CD8+ T cell responses has been aroused by the discovery of their efficacy in controlling simian immunodeficiency virus (SIV) infection in a vaccine model. The development of vaccines and immunotherapies utilizing human MHC-E (HLA-E)–restricted CD8+ T cell response requires an understanding of the pathway(s) of HLA-E transport and antigen presentation, which have not been clearly defined previously. We show here that, unlike classical HLA class I, which rapidly exits the endoplasmic reticulum (ER) after synthesis, HLA-E is largely retained because of a limited supply of high-affinity peptides, with further fine-tuning by its cytoplasmic tail. Once at the cell surface, HLA-E is unstable and is rapidly internalized. The cytoplasmic tail plays a crucial role in facilitating HLA-E internalization, which results in its enrichment in late and recycling endosomes. Our data reveal distinctive transport patterns and delicate regulatory mechanisms of HLA-E, which help to explain its unusual immunological functions.
Phenotypic and Genotypic Adaptation of <i>Escherichia coli</i> to Thermal Stress is Contingent on Genetic Background
Authors: Tiffany N Batarseh, Sarah N Batarseh, Alejandra Rodríguez-Verdugo, Brandon S Gaut
Journal: Molecular Biology and Evolution (2023)

Abstract Evolution can be contingent on history, but we do not yet have a clear understanding of the processes and dynamics that govern contingency. Here, we performed the second phase of a two-phase evolution experiment to investigate features of contingency. The first phase of the experiment was based on Escherichia coli clones that had evolved at the stressful temperature of 42.2 °C. The Phase 1 lines generally evolved through two adaptive pathways: mutations of rpoB, which encodes the beta subunit of RNA polymerase, or through rho, a transcriptional terminator. We hypothesized that epistatic interactions within the two pathways constrained their future adaptative potential, thus affecting patterns of historical contingency. Using ten different E. coli Founders representing both adaptive pathways, we performed a second phase of evolution at 19.0 °C to investigate how prior genetic divergence or adaptive pathway (rpoB vs. rho) affects evolutionary outcomes. We found that phenotype, as measured by relative fitness, was contingent on founder genotypes and pathways. This finding extended to genotypes, because E. coli from different Phase 1 histories evolved by adaptive mutations in distinct sets of genes. Our results suggest that evolution depends critically on genetic history, likely due to idiosyncratic epistatic interactions within and between evolutionary modules.
Antibody response to SARS-CoV-2 WT and Omicron BA.4/5 of inactivated COVID-19 vaccine in patients with lung cancer after second and booster immunization
Authors: Chen Chen, Liyuan Dai, Cuiling Zheng, Haolong Li, Xiaomeng Li, Mengwei Yang, Ruyun Gao, Jiarui Yao, Zhishang Zhang, Yuankai Shi, Xiaohong Han
Journal: Journal of Hematology & Oncology (2023)

Abstract COVID-19 inactivated vaccine-induced humoral responses in patients with lung cancer (LCs) to SARS-CoV-2 wild-type (WT) strain and variants BA.4/5 after the primary 2-dose and booster vaccination remained unknown. We conducted a cross-sectional study in 260 LCs, 140 healthy controls (HC) and additional 40 LCs with serial samples by detecting total antibodies, IgG anti-RBD and neutralizing antibodies (NAb) toward WT and BA.4/5. SARS-CoV-2-specific antibody responses were augmented by the booster dose of inactivated vaccines in LCs, whereas they were lower than that in HCs. Enhanced humoral responses waned over time after triple injection, notably in NAb against WT and BA.4/5. The NAb against BA.4/5 was much lower than WT. Age ≥ 65 was risk factor for immunization of NAb to WT. Undergoing treatment resulted in a lower antibody response than those without and radiotherapy was a also risk factor for seroconversion of NAb to WT. Lower lymphocyte counts contributed to a lower titer of IgG anti-RBD and NAb against BA.4/5 in LCs than HCs. Specifically, total B cells, CD4 + T cells and CD8 + T counts were correlated with the humoral response. These results should be taken into consideration for the elderly patients under treatment.
Myeloid-like tumor hybrid cells in bone marrow promote progression of prostate cancer bone metastasis
Authors: Xinyu Ye, Xin Huang, Xing Fu, Xiao Zhang, Risheng Lin, Wen Zhang, Jian Zhang, Yi Lu
Journal: Journal of Hematology & Oncology (2023)

Abstract Background Bone metastasis is the leading cause of death in patients with prostate cancer (PCa) and currently has no effective treatment. Disseminated tumor cells in bone marrow often obtain new characteristics to cause therapy resistance and tumor recurrence. Thus, understanding the status of disseminated prostate cancer cells in bone marrow is crucial for developing a new treatment. Methods We analyzed the transcriptome of disseminated tumor cells from a single cell RNA-sequencing data of PCa bone metastases. We built a bone metastasis model through caudal artery injection of tumor cells, and sorted the tumor hybrid cells by flow cytometry. We performed multi-omics analysis, including transcriptomic, proteomic and phosphoproteomic analysis, to compare the difference between the tumor hybrid cells and parental cells. In vivo experiments were performed to analyze the tumor growth rate, metastatic and tumorigenic potential, drug and radiation sensitivity in hybrid cells. Single cell RNA-sequencing and CyTOF were performed to analyze the impact of hybrid cells on tumor microenvironment. Results Here, we identified a unique cluster of cancer cells in PCa bone metastases, which expressed myeloid cell markers and showed a significant change in pathways related to immune regulation and tumor progression. We found that cell fusion between disseminated tumor cells and bone marrow cells can be source of these myeloid-like tumor cells. Multi-omics showed the pathways related to cell adhesion and proliferation, such as focal adhesion, tight junction, DNA replication, and cell cycle, were most significantly changed in these hybrid cells. In vivo experiment showed hybrid cells had a significantly increased proliferative rate, and metastatic potential. Single cell RNA-sequencing and CyTOF showed tumor-associated neutrophils/monocytes/macrophages were highly enriched in hybrid cells-induced tumor microenvironment with a higher immunosuppressive capacity. Otherwise, the hybrid cells showed an enhanced EMT phenotype with higher tumorigenicity, and were resistant to docetaxel and ferroptosis, but sensitive to radiotherapy. Conclusion Taken together, our data demonstrate that spontaneous cell fusion in bone marrow can generate myeloid-like tumor hybrid cells that promote the progression of bone metastasis, and these unique population of disseminated tumor cells can provide a potential therapeutic target for PCa bone metastasis.
Single-molecule methylation profiles of cell-free DNA in cancer with nanopore sequencing
Authors: Billy T Lau, Alison Almeda, Marie Schauer, Madeline McNamara, Xiangqi Bai, Qingxi Meng, Mira Partha, Susan M Grimes, HoJoon Lee, Gregory M Heestand, Hanlee P Ji
Journal: Genome Medicine (2023)

Epigenetic characterization of cell-free DNA (cfDNA) is an emerging approach for detecting and characterizing diseases such as cancer. We developed a strategy using nanopore-based single-molecule sequencing to measure cfDNA methylomes. This approach generated up to 200 million reads for a single cfDNA sample from cancer patients, an order of magnitude improvement over existing nanopore sequencing methods. We developed a single-molecule classifier to determine whether individual reads originated from a tumor or immune cells. Leveraging methylomes of matched tumors and immune cells, we characterized cfDNA methylomes of cancer patients for longitudinal monitoring during treatment.
p53 Oligomerization Domain Mutants: A New Class of Mutants That Retain “License to Kill”
Authors: David Stieg, Kaitlyn Casey, Maureen E. Murphy
Journal: Cancer Discovery (2023)

Summary: In this issue of Cancer Discovery, companion articles from the Prives and Lozano groups describe functional analyses of a common dimeric mutant of p53 found in Li–Fraumeni disease and sporadic cancer: A347D (AD). The authors show that the AD mutant is completely defective for canonical p53 transcriptional function, but interestingly retains some tumor suppressor function, which they show is manifested as “neomorphic” activities in transcription and the control of mitochondrial metabolism. See related article by Gencel-Augusto et al., p. 1230 (7). See related article by Choe et al., p. 1250 (6).
MDM2-PROTAC versus MDM2 Inhibitors: Beyond p53 Reactivation
Authors: Sylvain Peuget, Galina Selivanova
Journal: Cancer Discovery (2023)

Summary: In this issue of Cancer Discovery, Adams and colleagues present the discovery of a potent PROTAC, MDM2 degrader, which activates wild-type p53 leading to cancer cell death. Importantly, in a number of in vitro and in vivo experiments, the authors show that the depletion of MDM2 by PROTAC kills p53-mutant or p53-null cancer cells. See related article by Adams et al., p. 1210 (5).
Eligibility criteria and Enrollment of a Diverse Racial and Ethnic population in Multiple Myeloma Clinical Trials
Authors: Bindu Kanapuru, Laura Fernandes, Andrea C Baines, Rachel Ershler, Vishal Bhatnagar, Elizabeth Pulte, Thomas Gwise, Marc R. Theoret, Richard Pazdur, Lola A. Fashoyin-Aje, Nicole Gormley
Journal: Blood (2023)
Resolving the Pathogenesis of Anaplastic Wilms Tumors through Spatial Mapping of Cancer Cell Evolution
Authors: Bahar Rastegar, Natalie Andersson, Alexandra Petersson, Jenny Karlsson, Subhayan Chattopadhyay, Anders Valind, Caroline Jansson, Geoffroy Durand, Patrik Romerius, Karin Jirström, Linda Holmquist Mengelbier, David Gisselsson
Journal: Clinical Cancer Research (2023)

Abstract Purpose: While patients with intermediate-risk (IR) Wilms tumors now have an overall survival (OS) rate of almost 90%, those affected by high-stage tumors with diffuse anaplasia have an OS of only around 50%. We here identify key events in the pathogenesis of diffuse anaplasia by mapping cancer cell evolution over anatomic space in Wilms tumors. Experimental Design: We spatially mapped subclonal landscapes in a retrospective cohort of 20 Wilms tumors using high-resolution copy-number profiling and TP53 mutation analysis followed by clonal deconvolution and phylogenetic reconstruction. Tumor whole-mount sections (WMS) were utilized to characterize the distribution of subclones across anatomically distinct tumor compartments. Results: Compared with non-diffuse anaplasia Wilms tumors, tumors with diffuse anaplasia showed a significantly higher number of genetically distinct tumor cell subpopulations and more complex phylogenetic trees, including high levels of phylogenetic species richness, divergence, and irregularity. All regions with classical anaplasia showed TP53 alterations. TP53 mutations were frequently followed by saltatory evolution and parallel loss of the remaining wild-type (WT) allele in different regions. Morphologic features of anaplasia increased with copy-number aberration (CNA) burden and regressive features. Compartments demarcated by fibrous septae or necrosis/regression were frequently (73%) associated with the emergence of new clonal CNAs, although clonal sweeps were rare within these compartments. Conclusions: Wilms tumors with diffuse anaplasia display significantly more complex phylogenies compared with non-diffuse anaplasia Wilms tumors, including features of saltatory and parallel evolution. The subclonal landscape of individual tumors was constrained by anatomic compartments, which should be considered when sampling tissue for precision diagnostics.
A Multifunction Hydrogel‐Coating Engineered Implant for Rescuing Biofilm Infection and Boosting Osseointegration by Macrophage‐Related Immunomodulation
Authors: Yao Ding, Genhua Liu, Shaopeng Liu, Xuan Li, Kun Xu, Peng Liu, Kaiyong Cai
Journal: Advanced Healthcare Materials (2023)

Innovative methodologies combined with scavenging reactive oxygen species (ROS), alleviating oxidative stress damage and promoting macrophage polarization to M2 phenotype may be ideal for remodeling implant-infected bone tissue. Herein, a functionalization strategy for doping Tannic acid-d-tyrosine nanoparticles with photothermal profile into the hydrogel coating composed of konjac gum and gelatin on the surface of titanium (Ti) substrate is accurately constructed. The prepared hydrogel coating exhibits excellent properties of eliminating biofilm and killing planktonic bacteria, which is based on increasing susceptibility to bacteria by the photothermal effect, biofilm-dissipation effect of D-tyrosine, as well as the bactericidal effect of tannic acid. In addition, the modified Ti substrate has effectively alleviated proinflammatory responses by scavenging intracellular excessive ROS and guiding macrophages polarization toward M2. More interesting, conditioned medium from macrophage indicates that paracrine is conducive to osteogenic proliferation and differentiation of mesenchymal stem cells. Results from rat model of femur infection in vivo demonstrate that the modified Ti implant significantly eliminates the residual bacteria, relieves inflammation, mediates macrophage polarization, and accelerates osseointegration. Altogether, this study exhibits a new perspective for the development of advanced functional implant with great application potential in bone tissue regeneration and repair.
Clinical trials reimagined
Authors: Paul Y. Kwo, Tushar Patel
Journal: Hepatology (2023)

Clinical trials have been a central driver of change and have provided the evidence base necessary to advance new therapies for liver diseases. This review provides a perspective on the status of trials in hepatology and a vantage point into the emerging capabilities and external forces that will shape the conduct of clinical trials in the future. The adaptations to clinical trial operations in response to the disruptions by the COVID-19 pandemic and opportunities for innovation in hepatology trials are emphasized. Future trials in hepatology will be driven by unmet therapeutic needs and fueled by technological advances incorporating digital capabilities with expanded participant-derived data collection, computing, and analytics. Their design will embrace innovative trial designs adapted to these advances and that emphasize broader and more inclusive participant engagement. Their conduct will be further shaped by evolving regulatory needs and the emergence of new stakeholders in the clinical trials ecosystem. The evolution of clinical trials will offer unique opportunities to advance new therapeutics that will ultimately improve the lives of patients with liver diseases.
Rivaroxaban versus nadroparin for thromboprophylaxis following thoracic surgery for lung cancer: A randomized, noninferiority trial
Authors: Mengmeng Zhao, Yi Bao, Chao Jiang, Linsong Chen, Lisha Xu, Xiaogang Liu, Jiaqi Li, Yang Yang, Gening Jiang, Jian Li, Yunlang She, Qiankun Chen, Lei Shen, Chang Chen
Journal: American Journal of Hematology (2023)

The benefit of rivaroxaban in thromboprophylaxis after oncologic lung surgery remains unknown. To evaluate the efficacy and safety of rivaroxaban, patients who underwent thoracic surgery for lung cancer were enrolled, and randomly assigned to rivaroxaban or nadroparin groups in a 1:1 ratio; anticoagulants were initiated 12-24 h after surgery and continued until discharge. Four hundred participants were required according to a noninferiority margin of 2%, assuming venous thromboembolism (VTE) occurrence rates of 6.0% and 12.6% for patients in the rivaroxaban and nadroparin groups, respectively. The primary efficacy outcome was any VTE during the treatment and 30-day follow-up periods. The safety outcome was any on-treatment bleeding event. Finally, 403 patients were randomized (intention-to-treat [ITT] population), with 381 included in per-protocol (PP) population. The primary efficacy outcomes occurred in 12.5% (25/200) of the rivaroxaban group and 17.7% (36/203) of the nadroparin group (absolute risk reduction, -5.2%; 95% confidence interval [CI], [-12.2-1.7]), indicating the noninferiority of rivaroxaban in ITT population. Sensitivity analysis was performed in the PP population and yielded similar results, confirming the noninferiority of rivaroxaban. In the safety analysis population, the incidence of any on-treatment bleeding events did not differ significantly between the groups (12.2% for rivaroxaban vs. 7.0% for nadroparin; relative risk [RR], 1.9; 95% CI, [0.9-3.7]; p = .08), including major bleeding (9.7% vs. 6.5%; RR, 1.6 [95% CI, 0.9-3.7]; p = .24), and nonmajor bleeding (2.6% vs. 0.5%; RR, 5.2 [95% CI, 0.6-45.2]; p = .13). Rivaroxaban for thromboprophylaxis after oncologic lung surgery was shown to be noninferior to nadroparin.